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Compound mutants for retinoic acid receptor (RAR) beta and RAR alpha 1 reveal developmental functions for multiple

J Luo1, H M Sucov, J A Bader

  • 1Department of Biochemistry, Medicine and Oncology, McGill University, Montréal, Québec, Canada.

Mechanisms of Development
|March 1, 1996
PubMed

Insights

Mice lacking both retinoic acid receptor alpha 1 and beta genes showed severe developmental defects and early death. These findings highlight critical roles for these receptors in vertebrate development.

Area of Science:

  • Developmental Biology
  • Molecular Endocrinology
  • Genetics

Background:

  • Retinoic acid receptors (RARs) are crucial nuclear receptors mediating retinoid signaling.
  • Understanding RAR function is vital for comprehending vertebrate development and congenital malformations.

Purpose of the Study:

  • To investigate the specific roles of RAR alpha 1 and RAR beta isoforms in vertebrate development.
  • To identify phenotypes of double mutant mice lacking both RAR alpha 1 and RAR beta.

Main Methods:

  • Generation of genetically engineered mice with targeted disruptions in RAR alpha 1 and RAR beta genes.
  • Phenotypic analysis of single and double mutant mice, including histological examination of fetuses.
  • Assessment of susceptibility to retinoic acid (RA) teratogenicity.

Main Results:

  • Mice lacking both RAR alpha 1 and RAR beta exhibited perinatal lethality due to hypoxia.
  • Double mutants displayed congenital malformations in eyes, skull, respiratory tract, heart, great vessels, and urogenital system, resembling those in vitamin A deficiency.
  • Specific defects including hypoplastic lungs, bone fusion, ectopic thymus, and testicular abnormalities were observed.

Conclusions:

  • RAR alpha 1 and RAR beta isoforms play essential, non-redundant roles in embryonic development.
  • Combined loss of RAR alpha 1 and RAR beta leads to severe, multi-systemic developmental defects.
  • These receptors are critical for normal development, and their absence mimics aspects of vitamin A deficiency.

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